- CASE FILE
For over 25 years now, my overall health continues to decline from chronic malabsorption due to my birth defect - Cat Eye Syndrome.
ABOUT THIS CASE FILE
Baby History & Symptoms: My family's physician suspected a likely birth defect – seeing ear tags and, more importantly, no fecal evacuation – and transferred me to Wesley Medical Center in Wichita, Kansas, on November 5, 1977. Under the care of pediatric surgeon, Dr. Medo Mirza, I underwent five surgeries in his first year of life.
• The initial blood work done to determine the type of birth defect that occurred detected Trisomy 21 (Downs Syndrome). However, Dr. Mirza did not see the signature physical features of Downs in me, so he ordered more extensive blood work to more accurately pinpoint the diagnosis. Pediatric geneticist, Dr. Sechin Cho, performed and analyzed the testing and diagnosed me with Trisomy 22, a rare chromosomal birth defect. According to Dr. Cho, I was the first baby to survive out of six in the U.S. as of November 1977. I am the only member in my immediate family of seven that has a birth defect. I have three older brothers and a younger brother, all married with healthy children.
• I had a colostomy performed on November 7, 1977, and had it opened on November 9, 1977.
• I had double hernia repair done on November 23, 1977.
• I had my nonfunctioning right kidney and appendix removed on January 13, 1978. Dr. Mirza removed my appendix to prevent any future issues it might cause.
• I had a kidney stone removed from my left kidney during exploratory surgery on June 2, 1978.
• I had a corrective pull-through surgery performed on August 18, 1978. Five months after the surgery, I abruptly started crying with every bowel movement and developed a rash around my anorectal opening. Dr. Mirza stretched the anorectal opening and prescribed a muscle relaxant, neither were successful. With Dr. Mirza’s approval, my family found an alternative remedy called Bentonite that coated the intestinal lining. It soon stopped the crying and eliminated the rash by the third day. With the aid of Bentonite, I did not experience any more significant gastrointestinal issues until age 13.
Current History & Symptoms: Around age 13, I abruptly started experiencing digestive issues with foods that had a moderate amount of sugar in them, resulting in diarrhea and overwhelming the efficacy of the Bentonite. I eliminated most sugars from my diet to avoid diarrhea. However, other food sources started causing me diarrhea and other diarrhea-related symptoms that have persisted over the last 25-plus years – abdominal pain (always centered over his navel), anorectal pressure, and longer evacuation times (2 hours or more). I eliminated those food sources to avoid those symptoms. I tried a myriad of other nonprescription medications with limited success. Even though I did my best to manage my digestive health, it started to severely alter my ability to sustain employment and enjoy hobbies and activities. I applied for disability in early 2011 and scheduled an appointment with my primary care doctor, Dr. James Ratzlaff. Even with him overseeing my care and referring me to GI specialists, my GI tract has become sensitive to more than just food now.
• Inability to absorb or able to absorb only in small amounts – sugar, Vitamin C/citric acid/hydrochloric acid, protein/amino acids, dietary fiber, plant extracts, fats/fatty acids, spices, iron, and sodium.
• Oral and topical product sensitivities include hand sanitizers, mouthwashes, toothpastes, deodorants, soaps, shampoos, laundry detergent, antiseptics, and bandages.
• Current diet consists of pasta - American Beauty large elbow macaroni/elbow macaroni/rotini (1 gram of sugar and 25% Daily Value of folic acid) and Great Value eggless wide noodles/ribbons (2 grams of sugar and 30% Daily Value of folic acid), Hiland 2% milk (1 cup) diluted with tap/faucet water (2 cups), toasted wheat bread (1 piece), and tap/faucet water. Daily intake of 19 grams of sugar or less is all my intestinal lining can tolerate.
Etiology & Diagnostics: My digestive health has perplexed all the GI specialists he has seen. I have undergone thorough evaluation of my GI tract that has not produced any significant findings for the causes of my continual health decline. The myriad of medications prescribed to me all eventually produced the same symptoms as foods did. Genetic testing has consistently revealed a marker chromosome that could be the origin of my digestive decline.
• Normal blood work and metabolic panels continually remain within the normal ranges, with the exception of RBC, hemoglobin, and hematocrit sometimes falling a little under the norm. Dr. Ratzlaff concluded, "Since his blood work and metabolic panels always come back normal, there must be something underlying genetically that plays a role in his digestive decline." He added on May 23, 2019, "With a very restrictive and declining diet, many patients would be showing serious and detrimental symptoms and illness. Although he suffers GI symptoms, he amazingly remains relatively healthy otherwise. Medically, he is a complex mystery and what I call a 'freak of nature'."
• EKG in May 2019 revealed a pulse rate of 34 beats per minute.
• Medications prescribed by Dr. Ratzlaff and other doctors that I have tried – Bentyl, Amitriptyline, Tramadol, Mirtazapine, Hyoscyamine, Pantoprazole, Lexapro, Buspirone, Doxepin, Omeprazole, Ranitidine, Nifedipine, Proctosol, and Carafate. All these medications ended up adversely impacting my GI tract - abdominal pain, anorectal pressure, and loose stools/diarrhea.
• Current nonprescription medicine – Chromium Picolinate (daily – 100 micrograms) to help limit the sugar impacts in my GI tract, natural Vitamin E (daily – 200 International Units) to stimulate sufficient blood flow through my GI tract, and Advil (prn – 200 milligrams) to control the stress created from my malabsorption symptoms.
• A blood karyotype drawn in June 2011 revealed a supernumerary bi-satellited marker chromosome with 80% mosaicism.
• An upper GI X-ray ordered by an internal medicine surgeon and done on November 7, 2011, showed partial intestinal malrotation of the duodenal C-loop and visual small bowel all being right of the midline but without obstruction.
• A blood microarray revealed three chromosome alterations – partial tetrasomy 22q11.1q11.21 (Cat Eye Syndrome – multiple genes), a run of homozygosity on 7p15.3p14.3, and a partial microdeletion of 2p16.3 (NRXN1 gene) in April 2012. The genetic alterations on chromosome 2 and 7 have so far not revealed any connection to my malabsorption issues.
• I had a genetic counseling session following my microarray with a genetic counselor at Wesley on May 31, 2012. Her findings revealed that the two extra copies found on chromosome 22 attached together to form the marker chromosome.
• A digital rectal exam done on August 1, 2014, by a colorectal surgeon in Wichita produced a diagnosis of proctalgia fugax. I underwent 26 sessions of physical therapy in 2014-2015 that helped strengthen my bowel control somewhat.
• A number of tests and procedures done in February and April 2018 by the University of Nebraska’s Intestinal Rehabilitation Program (IRP) – abdominal ultrasound, small bowel series, extensive blood work, and upper and lower scopes with biopsies – only reconfirmed intestinal malrotation without obstruction, leaving the team at one of the premier GI facilities in the country without further recommendations or referrals.
• A duodenal C-loop tissue biopsied for a karyotype/FISH analysis on April 25, 2018, revealed 100% tetrasomy of 22q11.1q11.21 (Cat Eye Syndrome) during metaphase and 75.5% tetrasomic mosaicism during interphase.
• I saw a geneticist - Dr. Omar Abdul-Rahman - following my karyotype/FISH at the University of Nebraska on September 4, 2018. His findings suggest that my symptoms appear to be consistent with absorption and/or transport across the intestinal lining, although my genetic results have not established a clear etiology for that yet. However, he offered possible explanations for my symptoms – the percentage of intestinal mosaicism, the impact of the increased expression of the genes within the tetrasomic region, the downstream effects of genomic change on other genes outside the tetrasomic region, and/or the effect of time on mosaicism.
• I applied to the Undiagnosed Diseases Network (UDN) in November 2018, hoping to be accepted into their program for medical evaluation. Because I already had a diagnosis, I received a rejection letter from them on February 7, 2019. They acknowledged in the rejection letter that my CES is the source of my malabsorption issues, stating, “Given that Mr. Durst has a diagnosis of Cat Eye Syndrome, and his gastrointestinal symptoms are most likely caused by this condition, he does not meet enrollment criteria for the UDN.”
• In an e-mail reply on April 19, 2019, Dr. Lori Erby, a genetic counselor at John Hopkins University and at the National Institute of Health (NIH), speaking on Dr. Francis Collins’s behalf, the NIH Medical Director, seconded UDN’s medical assessment, “Cat Eye Syndrome is known to be very variable in how it presents, and some other individuals have reported GI symptoms. It does seem likely that this is a result of the extra chromosomal material.”
• A whole genome sequencing (WGS) blood sample taken on March 4, 2019, revealed a genetic variant of unknown significance (VUS) on the POLG gene located on chromosome 15q26.1. It is associated with autosomal recessive mitochondrial DNA depletion syndrome 4B (MNGIE type – mitochondrial neurogastrointestinal encephalopathy). The abnormal genetic variant is a missense mutation, or substitution, with the DNA letter C (cytosine) replacing the letter T (thymine). However, I do not have the primary symptoms of MNGIE – progressive external ophthalmoplegia and axonal sensory ataxic neuropathy. Furthermore, a recessive condition needs two abnormal genetic variants of the same gene to be confirmed. With no confirmed second genetic variant and a lack of the primary symptoms of MNGIE, Veritas Genetics could not conclusively say that this VUS on the POLG gene is causing my malabsorption.
• I saw Dr. Rahman for another genetic counseling session on July 12, 2019, regarding my WGS results. Since I do not exhibit the primary symptoms of MNGIE and only have one confirmed genetic variant of the POLG gene, he stated the VUS is probably only having a secondary role regarding my malabsorption issues. Because I exhibit some primary symptoms of CES (imperforate anus/anal atresia and ear tags/tabs), have multiple genes in my tetrasomic chromosome 22 region that are involved in mitochondria function and activity, and the high tetrasomy that exists in my duodenal C-loop, he emphasized the CES is most likely the primary source of my malabsorption issues. He explained that with the tetrasomy most likely playing a role in mitochondria dysfunction, my body looks to the POLG gene to overcompensate and produce more good mitochondria (mitochondria DNA – mtDNA) to offset the tetrasomic mtDNA cells. Therefore, it puts stress and pressure on the POLG gene to where it cannot keep up with the demand to supply enough good mitochondria I need for my body to run at full optimization and capacity to overcome the tetrasomic mitochondria, causing more GI dysfunction and deterioration. Furthermore, less mitochondrial DNA is produced as a person ages, adding to the increased GI dysfunction and deterioration as I age. He believes a PICC line could be beneficial for me, but ruled out a G-tube (feeding tube) that would send nutrition straight into my digestive tract. He believes a PICC line would determine whether my malabsorption is restricted only to the GI tract or is a systemic issue, impacting my entire body.
Overall Perspective: I strongly feels my birth defect is responsible for my digestive decline. I have made this assessment. I believe the tissue metaphase result (100% tetrasomy) explains why my digestive health continues to decline, while the tissue interphase result (75.5% tetrasomy) explains why I still have some absorptive capacity left. Therefore, I have developed this hypothesis regarding my digestive decline – as the mosaicism/percentage of tetrasomy keeps rising, my diet keeps shrinking. When I asked Dr. Rahman about my hypothesis, he told me him that is “reasonably credible.” Dr. Ratzlaff agrees with this. l asked Dr. Rahman what reason would cause the tetrasomic cells to have a competitive advantage over the disomic (normal) cells. He told me that some studies show that increased expression of microRNA genes can provide a growth advantage to some cell lines, and two known ones (MIR648 and MIR3198-1) exist within my tetrasomic region. I have voiced alarm about the recent increased speed of my digestive and overall decline to many doctors, geneticists, and researchers around the country and feel time is of the essence to help me find answers to better health. I have concerns that alternative mechanisms of digestive alimentation, including a PICC line (parenteral nutrition - PTN), will cause the same symptoms as most oral intake does due to the amount of mosaicism (80%) detected in my blood. I have taken a very proactive approach in my health to find answers and treatments by doing extensive research on chromosome 22 and the genes in the tetrasomic region as it relates to my malabsorption issues. I have reached out to many geneticists and researchers across the country and the globe for a potential individual research study (N of 1 study) looking into the impact my birth defect is having on my malabsorption issues. While some have replied, none of them have offered to study me. Christopher Lengner, an associate director at the Institute for Regenerative Medicine at the University of Pennsylvania, told me in an e-mail reply on June 7, 2019, "At a high level, the strategy that seems most tractable to gain some better understanding of the GI symptoms is to try to culture, side by side, intestinal tissue from your normal cells vs. the tetrasomic cells and then perform an unbiased profile of gene expression, then use existing (and relatively straightforward) analysis approaches to determine what pathways are altered between the two, then determine whether there may exist molecules or approaches to change those pathways in a directions towards the normal." I believe an extensive review of the tetrasomic genes and how they are dominating the normal cells within the intestinal lining may provide clues for potential digestive improvement and overall well-being. Dr. Rahman strongly emphasizes and encourages that collaboration between geneticists, genetic researchers, and GI specialists is needed and necessary to find specific answers and treatments to improve and turnaround my digestive and overall health.
Opportunity and Records: I am asking you, "Chasing The Cure," to consider my case file for the TV series. I want to leave no stone unturned in my journey to better health, and this is an opportunity I see to tell the world my story living with a rare birth defect and the impacts and consequences of it. I want to provide others watching and listening to my story that I will keep fighting as long as I live, not to give up, and keep pursuing and persevering. I believe anyone living with a rare and/or undiagnosed condition deserves the best care possible and the right to live a full life. Back in 2004, I had applied to ABC's Extreme Makeover to have my crooked teeth and asymmetrical jaw corrected. My birth defect caused these physical anomalies. Even though I was not accepted on the show, I received a call a year later from my childhood dentist. He heard I had applied to the show, and if accepted on the show, he was willing to cover the travel expenses. When I told him I had not been accepted, he asked me if I still wanted to get my jaw fixed. I acknowledged to him that I did. He covered all the major expenses of my jaw surgery. Moreover, the orthodontist donated his time and did not charge my childhood dentist for any orthodontic work expense incurred, and the oral surgeon reduced some of the cost of the jaw surgery. I see this TV series as another outlet, lead, and opportunity to potentially better my health. Even if accepted to the show and no genetic and/or medical breakthrough, maybe somebody watching - a doctor, another patient, and/or an interested viewer - can help lead me to better health or know of someone or some medical organization and/or facility that can lead me to better health. I have received all of my pertinent adult medical records. Although I could not retrieve my baby medical records, I have found information online and through human sources to my past that compensate for not recovering my baby records. All the records and information should be beneficial to your efforts in gaining perspective surrounding the mystery of my health. Sincerely, I hope you consider my file case.